Indiana University-Purdue University Indianapolis (IUPUI) / Children's and adolescents' capacity to provide valid informed consent is one of the key ethical concerns in pediatric research, and the focus of this project. The original contribution to knowledge is the advancement of both conceptual and empirical bioethical approaches to research with vulnerable populations. First, a review of adolescent vulnerability is presented to highlight the complex interplay between capacity and other forms of vulnerability. This review is offered as an interdisciplinary analysis to better understand why the study of vulnerable populations is critical to the ethical advancement of clinical research. Results from this analysis suggest the need for enhanced screening techniques as well as the utilization of specialized staff to identify and reduce the impact of different forms of vulnerability. The primary tasks of the empirical portion of the dissertation were to: (1) Adapt a validated adult competency assessment tool for clinical research, the MacArthur Competency Assessment Tool for Clinical Research, to assess the capacity of children and adolescents to consent to clinical research; (2) Identify predictors that impact children and adolescents’ capacity to provide consent to clinical research; and (3) assess differences and similarities in capacity between healthy and chronically ill children and adolescents. Overall results suggest adolescent capacity to consent to research was similar to adults, and most strongly associated with their family's socioeconomic status as well as their level of health literacy. These findings contrast starkly with the age-based criterion for providing consent currently utilized in assent and consent determinations. These findings also provide insights into ways to ethically involve youth in complex biomedical research.